In each of 10 children with type 1 RTA, we have recently reported the attainment and maintenance of normal stature, even after previous stunting, when correction of acidosis was sustained with larger doses of alkali therapy (greater than 5 mEq/kg/day). Renal bicarbonate (RBW) necessitated this large dose. In each of 7 patients in whom adquate alkali therapy was started before age 3 years, nephrocalcinosis was not radiographically demonstrated at ages 7-17 years. These findings contrast sharply with those previously reported; with smaller doses of alkali (1-3 mEq/kg/day), stunting persists or occurs and nephrocalcinosis is predictable by age 5 years. Our 7 patients with classic RTA without apparent nephrocalcinosis and without measured reduction in GFR, evidence of urinary tract infection, impairment in somatic growth or requirement for potassium therapy, constitute a unique group of patients with type 1 RTA, who provide a special opportunity to study type 1 RTA, in relatively pristine state. In Part I, affected children will be investigated with respect to the occurrence, duration and physiological character of RBW, before, during and after the period of "catch-up" growth that attends the early course of corrective alkali therapy and during the increase in height velocity at normal adolescence. The data derived from these will permit more rapid and accurate assessment of therapeutic needs in these patients. Additionally, in these patients we will investigate the physiologic character of their renal disorder, during bicarbonate loading and during Na ion restriction. In Part II, we will investigate the metabolic and endocrinologic effects of hyperchloremic metabolic acidosis which may predispose to growth failure. In these patients, we will determine whether Na ion depletion predictably occurs during acidosis and whether it persists during partial correction of acidosis with alkali therapy of 3 mEq/kg/day. We will investigate the effect of acidosis on the circulating blood levels of growth hormone and somatomedin C and A, on the urinary excretion of collagen breakdown products and the plasma concentrations of enzymes active in the biosynthesis of collagen, and on the circulating levels of Vitamin D.